Protamine

Protamines are proteins derived from the sperm or testes of salmon or related fish. They are added [1] are added to insulinsNPH Neutral Protamine Hagedorn and PZI protamine zinc to delay their absorption.

The difference between isophane/NPH insulins and PZI insulins is the amount of protamine used; there is more in PZI than in NPH/isophane insulins. It's the extra protamine which makes the PZI a slow-acting insulin.[2]

The basis of absorption of any insulins containing protamine [3] is the breakdown of this protein by proteolytic enzymes [4] or proteases in the body. Only after this is accomplished can the insulin itself be absorbed. More protamine in the suspension means insulin absorption will be delayed longer; less protamine means the insulin will act faster.

Protamine, like insulin itself, is a protein. In the case of antibody formation, it is possible that the insulin itself is not the cause of them; the proteins present in the suspension, such as protamine, may be. [5] In this case, changing the type of suspension would solve the problem.